Stromal coexpression of uPA/PAI-1 protein predicts poor disease outcome in endocrine-treated postmenopausal patients with receptor-positive early breast cancer

Breast. 2019 Aug;46:101-107. doi: 10.1016/j.breast.2019.05.007. Epub 2019 May 3.


Background: To evaluate whether uPA/PAI-1 protein in hormone receptor-positive (HR+) breast tumor can predict prognosis in early breast cancer (BC).

Methods: 606 women with HR + BC who had ≥5 years of endocrine therapy and in whom tumor tissue was available were included in this analysis. Stromal uPA/PAI-1 protein expression was evaluated by immunohistochemistry and correlated with distant recurrence-free survival (DRFS) and overall survival (OS).

Results: Stromal uPA was detected in 292/538 tumors (54.3%) while 269/505 samples (53.3%) exhibited stromal PAI-1. Co-expression of both proteins was found in 163/437 (37.3%) samples. Stromal uPA/PAI-1 co-expression was not associated with tumor size, age, nodal status, grading, or receptor status. Tumor stroma with both uPA and PAI-1 protein expression were more likely to have a shorter DRFS (HR: 1.87; 95%CI 1.18-2.96; p = 0.007) and OS (HR: 1.29; 95%CI 0.93-1.80; p = 0.129) than women without uPA/PAI-1 co-expression. After a median follow-up of 10 years, women with uPA/PAI-1-positive tumors experienced a significantly shorter DRFS (86.5% vs 72.4%; p < 0.001) and OS (70.4% vs 58.9%; p = 0.020) compared to women with uPA/PAI-1 negative tumors.

Conclusion: Stromal co-expression of uPA and PAI-1 in breast cancer predicts poor DRFS and OS in postmenopausal women with HR + early-stage BC who receive endocrine therapy.

Keywords: Breast cancer; Immunohistochemistry; PAI-1; Prognosis; uPA.

Publication types

  • Evaluation Study

MeSH terms

  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor / genetics
  • Breast / cytology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality*
  • Disease-Free Survival
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Postmenopause
  • Prognosis
  • Risk Factors
  • Stromal Cells / metabolism
  • Treatment Outcome
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • ErbB Receptors
  • Urokinase-Type Plasminogen Activator